Frequently Asked Questions About Clinical Trials in Colombia

This is a compilation of the frequently asked questions we receive from our customers (aka sponsors) when exploring Colombia as a clinical trial destination.

We are looking for an investigator and a site to conduct our first-in-human trial, but we are not sure if Colombia is the right place. Can you help us?

Usually medical device companies in need of first-in-human/first-in-man (FIH/FIM) clinical trial help approach bioaccess.™ after they have identified a principal investigator (PI) in Colombia at an international conference or through their personal and business connections. This PI is usually someone who has demonstrated expertise in the intended use of the investigational device after presenting at international conferences or after publishing on recognized academic journals.

Only after the medical device company has been in direct contact with the PI and has decided to have him lead and conduct its (FIH/FIM) trial is when we at bioaccess.™ come in and operationalize the trial in Colombia. We contact the PI, gather IRB/EC requirements at the PI's hospital, we assemble the dossier package for IRB/EC submission, and then we apply for MoH (INVIMA) approval. We also help with the importation of the investigational devices and become the project managers and monitors of the study.

So, the choice of conducting a trial in Colombia is first driven by the medical device company's choice of a PI in Colombia. Asides from having the right PI leading your study in Colombia, the country’s advantages are in essence: a) fast MoH review (~30 days after submission and IRB/EC approval), b) cost savings (~30-50% savings over US hospital fees), and c) large patient pool (50 million people with universal health care).

If your company hasn’t found an investigator in Colombia who has expressed his interest in participating in your FIH trial, then we will have to find it for you —we offer site and PI selection services.

In a nutshell, what's the process to get a clinical trial approved in Colombia?

Select a site from the 110+ GCP-government-certified clinical research centers in Colombia.

Can healthy volunteers participate in phase I clinical trials in Colombia?

No. Colombian regulations prevent healthy volunteers from participating in Phase I trials; only sick patients with the disease related to the therapeutic area of your investigational products are allowed.

How many institutional review boards (IRB) are there in Colombia?

As of September, 2018, Colombia's INVIMA there are 69 IRBs (also known as “research ethics committees” (EC) in Colombia) that INVIMA has certified in Good Clinical Practice following ICH/GCP international guidelines. Every site in Colombia can only be associated with one IRB/EC at any point in time.

We have a medical device at the R&D (no approval by any regulatory body) stage and we want to know what type of biocompatibility testing would be sufficient for a Colombian IRB to approve a clinical study. Specifically, we would like to know if a systemic toxicity (90 day sub-chronic in rats) or an animal study (dog) would sufficient to show safety prior to proceeding with a clinical study in Colombia.

Every IRB/EC in Colombia has its own set of requirements to approve a clinical study. You should first select the site where you plan to conduct your study, have them tell you the IRB they are associated with, and have a pre-submission meeting with the IRB to let them tell you if the animal data you have is considered sufficient for study approval. IRBs in Colombia generally follow INVIMA's guidelines for the approval of a clinical study.

INVIMA has general requirements for animal data. INVIMA requires that the device’s direct patient risks be mitigated by doing device level tests (i.e., biocompatibility, strength test, corrosion test, traceability, etc.). It's up to the sponsor to prove to INVIMA the device's safety by providing as much documentation as the sponsor deems necessary. You can read INVIMA requirements to approve a medical device clinical study here.

How much does a medical device clinical trial in Colombia cost?

The cost to conduct a medical device clinical trial in Colombia is about 30-50% less than what it would cost to conduct the same trial in the US, Canada or Western Europe.

A medical device clinical trial project has five general cost components (in USD):

Study Design Fees: This includes the costs associated to designing your study and producing its respective documents (i.e., protocol, investigator's brochure, patient informed consent form, case report form). If you decide to outsource this activity to a contract research organization (CRO), then the cost varies depending on the complexity of the study, and it may range anywhere from 25,000 to 100,000.

CRO Fees: This includes site selection, institutional review board (IRB)/ethics committee (EC) and Ministry of Health (INVIMA) approval, trial set-up (i.e., clinical trial agreement (CTA) execution, site visit, import license), project management, study monitoring, etc. Depending on who you choose to render the study monitoring of your project, expect to pay about 700 per day for a monitoring visit. You should budget about 50,000 for CRO fees. See a sample CRO proposal here.

Hospital Fees: These fees will depend on the schedule of events in your study protocol. Every trial is different; it is difficult for a CRO to give you a ballpark price per patient without fully reviewing your study protocol and creating a proposed budget to present to the site for negotiation and approval.

I am planning to conduct an investigator-initiated trial (IIT) in Canada. I was given a cost of $8,000 to $10,000 per patient. Will this cost be lower in Colombia?

Sponsoring a clinical trial entails numerous regulatory responsibilities, including those set forth in 21 CFR 312 and 812. There is no “lite” version of sponsor responsibilities for sponsor-investigators.

Regardless of who sponsors/funds a trial (for investigator-initiated trials (IIT): a for-profit, non-profit, state, or federal agency; or for industry-sponsored trials (IST): a for-profit entity), you will likely receive from a site a detailed budget. Usually, when a site or an investigator gives you an approximated cost-per patient it only includes actual clinical costs based on the schedule of events on the protocol, and indirect costs (i.e., administrative fees related to start-up costs, an overhead of about 20%, study coordinator time, record storage, etc.).

The costs that an industry-sponsor typically saves on an IIT vs an IST are the following,

Study design (i.e., protocol creation and its accompanying documents including the case report form, the patient informed consent, and the investigator’s brochure)

Study monitoring cost

Data collection and statistical analysis cost

Medical writing and publication of the results

On an IIT, the study design/protocol is a) authored by the investigator within the course and scope of his/her university/hospital employment; or b) an investigator within the course and scope of his/her university employment jointly with an employee of another entity (e.g., an employee of another non-profit institution or an employee of the company funding the study). The same goes for the other costs that I mentioned above.

One of the greatest challenges for IIT is the contract negotiations toward a clinical trial agreement, which averages 70.5 days among the companies surveyed for a recent report by Cutting Edge Information, a Research Triangle Park, N.C.-based business management and consulting firm. The primary reasons for such elongated timelines: complicated contract review processes and complex negotiations and/or disagreements.

If you decide to conduct an IST, then your company will likely assume the cost of designing the study and authoring the protocol and its accompanying documents. This cost may be around $20-60k depending on the complexity of the study. You —the sponsor— will also have to assume the other costs that I mentioned above.

Once a life sciences company agrees to fund an IST, they are essentially spending money on a trial over which they have no control.

IIT clinical trial agreements (CTAs) are different from CTAs for ISTs for three main reasons:

The company does not have the sponsor’s regulatory responsibilities.

The investigator is asking for help from the company, instead of the other way around.

The investigational product is usually a marketed product (as in Phase IV studies).

The main areas of interest in IIT CTAs are the following:

Compliance with laws

Clearly specific who is the “sponsor” from a regulatory perspective.

Sponsor (i.e., PI and/or site, if site is contracting on PI behalf) must comply with applicable laws and regulations.

From industry perspective, helps ensure company can use data in FDA applications, if needed/desired.

Investigator and sponsor duties.

Data ownership rights.

Site/investigator typically owns data, but provides company with periodic and final reports.

Site/iInvestigator may provide a data license to company.

Intellectual Property (PI).

Publication:

Typically more liberal publication rights for investigator, although company may still review (and perhaps comment) and postpone for certain reasons.

Memorialize that investigator is “responsible party” for clinicaltrials.gov purposes.

Privacy (including HIPAA).

Confidentiality:

May or may not be mutual – companies often consider their interests in the study, what information they actual provide, and desired use of data and results.

Ex: Does the company want the ability to use the data in marketing submissions or otherwise?

Ex: Is the company supplying proprietary data to help develop study, or was the idea for the study completely the investigator’s?

Audit/Monitoring:

Investigator is the sponsor and is therefore responsible for monitoring from a regulatory standpoint.

Company may require audit/monitoring rights, depending upon level of company’s involvement.

Payments.

Serious adverse event (AE) reporting obligations:

Investigator is the sponsor and responsible for regulatory obligations.

In post-market context, company may be required to submit AEs if they are involved in the study.

Termination rights.

Indemnification:

Typically far more limited than in a regular CTA, but depends on company involvement with the study.

Ex: harms directly caused by company product (manufacturing defects/product liability); company use of study data.

Subject injury (it varies): No company reimbursement vs. injuries directly caused by a problem with company product (similar to indemnification) vs. broader, if company is more involved with the study.

Subject injury and indemnification —a major focus in most ISTs with experimental treatments— are typically smaller factors in IIT CTAs because the investigational product is usually a marketed product and the company does not want to accept liability for a study over which it has minimal control. Normally, the company warrants that the investigational product is manufactured per specifications, the investigator indemnifies the company for subject injury, and the company indemnifies the investigator-sponsor for possible commercialization.

If you decide to conduct a trial outside your home country you will have to plan for costs associated with shipping an importation, international travel, etc.

Every trial is different. It is almost impossible for anybody to give you an approximated cost per patient in Colombia without reading the protocol, identifying the schedule of events on it, putting together a budget grid, and contacting sites in Colombia for pricing.

We have been involved with trials in Colombia that range from $2,000 to $20,000 per patient in different therapeutic areas involving drugs and medical devices. Every trial is totally different from the other. All we can give you at this point (based on our own experience and from gathering international data) is approximated percentages of the savings that you will have when conducting a comparable trial in the US vs in Colombia.

What’s customary in IST is that the sponsor firsts presents a draft/proposed budget to a site (the sponsor sometimes hires the services of the CRO to create this budget), and then waits for the site to respond with a counteroffer. When you present a site a proposed budget, the site will look at it and will determine if it is willing to conduct the trial at your proposed prices or not; here is when the ping-pong game of budget negotiations begin until both parties agree on a final agreed-upon study budget that will be the genesis of a clinical trial agreement between the sponsor and the site.

What's the typical competent authority (INVIMA) cycle time for Colombia?

For medical devices, the INVIMA committee meets every 30 days. See their meeting schedule here. Approval takes about 30 days.

For pharmaceutical drugs, the INVIMA committee meets every 30 days. See their meeting schedule here. Approval takes about 10-12 months.

We are planning a trial in Colombia. We already have the site and principal investigator selected. How can you assist us?

If you have a site and principal investigator already selected in Colombia, we can assist you by providing you with our contract research organization (CRO) services in Colombia. We can help you with the trial set-up (e.g., budget and clinical trial agreement approved and executed, ethics committee and Ministry of Health/INVIMA submission, import license, logistics/storage/shipment to site, etc.). We can also help you with post-approval services (e.g., project/study management, site monitoring, medical writing, etc). Read more about our trial-set up services here.

Yes, but only the study budget (final). You do not have to submit your clinical trial agreement between your company and the site in Colombia. Please see the question and answer above for clinical trial approval requirements at INVIMA in Colombia.

Do I need a Good Laboratory Practices (GLP) certificate to get my drug trial approved in Colombia?

No. You will only need to provide your Good Manufacturing Practices (GMP) certificate. Please see the requirements for trial approval in Colombia here.

We are working on a stem cell project, and we are starting to look at sites for our first-in-human trial work. How difficult would it be to bring stem cells from the US into Colombia for the trail?

Easy! All we need is approval from the institutional ethics committee at the site to officially start recruiting patients. We will take care of the importation process. It should be pretty fast and straightforward.

What's the process to import investigational products into Colombia?

In order to legally import the investigational product and additional accessories named on the clinical supply list sent with your INVIMA submission, we must apply on your behalf —for each shipment— for a separate application for an import permit approval to the Ministry of Industry, Commerce and Tourism (VUCE office). The average processing time is between 5 to 10 business days.

Our product already has CE Marking, it already has marketing authorization from INVIMA, and we are already selling it in Colombia. We would like to conduct a trial on the product (for the same indication of use it is approved for) in Colombia so that we can obtain clinical data for an FDA PMA submission. Does that make our trial easier in Colombia?

Yes! All you have to do is find a clinical research site and get your study approved at its IRB/EC. INVIMA doesn't have to evaluate and approve your study (since you already have INVIMA approval to import your product into Colombia).

Will the FDA accept data from a clinical research site in Colombia?

Yes! For international inspections of pharmaceutical trials, the FDA requires conducting the trials according to GCP and under the Ethics Committee approval. For medical devices, the FDA requires the conduct of the trial according to the Declaration of Helsinki (a requirement by Colombian law in Resolution 2378) and to the laws and regulations of the country where the trial is taking place.

If a Colombian research site receives a Good Clinical Practice Certificate from INVIMA, then it is also compliant with FDA requirements for international inspections for studies involving investigational drugs and biologics as well as for studies involving investigational medical devices.

How long does it usually takes to get a new pharmaceutical drug developed and approved (from lab to market) in Colombia?

Drug development has two major phases: Pre-clinical and clinical. This phase involves testing the investigational product for safety, toxicity, pharmacokinetics, and metabolism in humans. The information that you gathered from this pre-clinical testing will be submitted to regulatory authorities (in Colombia, to INVIMA), as an Investigational New Drug application or IND. If the IND is approved, development moves to the clinical phase.

The clinical phase (i.e., clinical trials) involves three or four steps:

Phase I trials, usually in healthy volunteers, determine safety and dosing.

Phase II trials are used to get an initial reading of efficacy and further explore safety in small numbers of patients having the disease targeted by the investigational product.

Phase III trials are large, pivotal trials to determine safety and efficacy in sufficiently large numbers of patients with the targeted disease. If safety and efficacy are adequately proved, clinical testing may stop at this step and the investigational product advances to the new drug application (NDA) stage.

Phase IV trials are post-approval trials that are sometimes a condition attached by INVIMA, also called post-market surveillance studies.

It's is very difficult to determine how long this process will take in Colombia. The pre-clinical phase is entirely private and needs no government approval. So, the duration of this phase is entirely depending on your company's cash position, talent pool, and speed to conduct pre-clinical research. The clinical phase may take several years since you will have to conduct at least three clinical trials; each clinical trial may take anywhere from 1 to three years depending on the type of investigational product that you are developing.

Once you gather all the pre-clinical and clinical data, you will need to submit your NDA to INVIMA for approval. INVIMA may take 9-12 months to approve a new drug in the market.

We plan to conduct a non-interventional retrospective research study in Colombia. Which agency do we need to apply for ethics or IRB study waiver or exempt status?

You will need to submit your study documents for evaluation and approval at the institutional review board (IRB or also known as institutional ethics committee) that is associated with the site/center where you plan to conduct the study. Every hospital facility in Colombia has its own IRB/ethics committee. If you want to have an official letter from the regulatory agency saying that you are exempt from their jurisdiction, then you have to contact INVIMA and submit a derecho de petición request. You will get an answer from INVIMA within 30 business days.

What should I know about translations?

All documents must be translated to the "Colombian" Spanish dialect. The Spanish spoken in Latin America changes from country-to-country and INVIMA has rejected documents such as an Informed Consent Form that is not easily understood by an average native Colombian citizen.

We recommend that sponsors translate their documents by Colombian Spanish-speaking translators certified by the Colombian Ministry of Foreign Affairs.

A certified translator is a person who has passed the linguistic proficiency test from the relevant agency designated by the Government of Colombia for this purpose. Any translator who passes this test should take office before the Superior Tribunal of the Judiciary District and apply for a certification from the Ministry of Justice and Law, which will accredit him or her as an official certified translator. The certified translator must register his name with the Ministry of Foreign Affairs by submitting a copy of the Oath of Office and a copy of the certification issued by the Ministry of Justice and Law.

We offer our sponsors certified translation services and works with local Colombian certified translators duly endorsed by the Ministry of Foreign Affairs (who therefore, hold the relevant certification issued by the Ministry of Justice and Law) with past experience in the clinical research industry. This will ensure that our sponsor's translations as accurate, faithful and valid to be presented to any government agency such as INVIMA.

Although INVIMA doesn’t specifically require that sponsors submit documents translated to Spanish by official government-certified translators, it’s customary —and expected by the recipient of the document— in Colombia that all translations (both in private business and government dealings) are done by government-certified translators.

Just like there are differences in English expressions, spelling, industry and business terminology among English-speaking countries (USA, UK, Australia, Canada, etc.) Spanish varies throughout Latin America. Colombian Spanish has its own peculiarities just like Mexican or Argentinian Spanish have. For Colombia’s INVIMA purposes, this is important in two ways: a) the evaluation committee members should be able to easily understand the protocol, the investigator's brochure (IB), and all other study-related documents, and b) the patient's informed consent form (ICF) should be written in such a way that an average Colombian native citizen is able to easily understand (there have been cases where the committee has rejected ICFs for being written in non-Colombian Spanish).

A printed document that has been translated by a certified translator in Colombia will have (by law) the following elements:

A "Certified Translation" header.

A consecutive certified translation control number.

The seal of the official translator in which the translator's full name, his or her certification number issued by the Ministry of Justice, the certification issue date, and the languages that the translator is certified to translate.

The signature of the translator in the last page, or at least, the initials of the translator if the document has several pages.

Through a seal and a signature, the translator certifies that the translation is correct and complete and takes responsibility for what is translated. This way, the translator basically acts like a notary authenticating a document. A certified translator is also authorized to be an official interpreter, translating declarations and affidavits before a notary or a judge.